National Cancer Institute

Biological processes, including events necessary for life and those that lead to cancer, occur at the nanoscale. We are, in fact, composed of biological nanomachines. Nanotechnology provides researchers with the opportunity to study and manipulate macromolecules in real time and during the earliest stages of cancer progression. Nanotechnology can provide rapid and sensitive detection of cancer-related molecules, enabling scientists to detect molecular changes even when they occur only in a small percentage of cells. Nanotechnology also has the potential to generate entirely novel and highly effective therapeutic agents.

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Benefits for Diagnosis

Imaging: Current imaging methods can only readily detect cancers once they have made a visible change to a tissue, by which time thousands of cells will have proliferated and perhaps metastasized. And even when visible, the nature of the tumor—malignant or benign—and the characteristics that might make it responsive to a particular treatment must be assessed through biopsies. Imagine instead if cancerous or even pre-cancerous cells could somehow be tagged for detection by conventional scanning devices. Two things would be necessary—something that specifically identifies a cancerous cell and something that enables it to be seen—and both can be achieved through nanotechnology. For example, antibodies that identify specific receptors found to be overexpressed in cancerous cells can be coated on to nanoparticles such as metal oxides which produce a high contrast signal on Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans. Once inside the body, the antibodies on these nanoparticles will bind selectively to cancerous cells, effectively lighting them up for the scanner. Similarly, gold particles could be used to enhance light scattering for endoscopic techniques like colonoscopies. Nanotechnology will enable the visualization of molecular markers that identify specific stages and types of cancers, allowing doctors to see cells and molecules undetectable through conventional imaging.

Screening: Screening for biomarkers in tissues and fluids for diagnosis will also be enhanced and potentially revolutionized by nanotechnology. Individual cancers differ from each other and from normal cells by changes in the expression and distribution of tens to hundreds of molecules. As therapeutics advance, it may require the simultaneous detection of several biomarkers to identify a cancer for treatment selection. Nanoparticles such as quantum dots, which emit light of different colors depending on their size, could enable the simultaneous detection of multiple markers. The photoluminescence signals from antibody-coated quantum dots could be used to screen for certain types of cancer. Different colored quantum dots would be attached to antibodies for cancer biomarkers to allow oncologists to discriminate cancerous and healthy cells by the spectrum of light they see.

Benefits for Treatment and Clinical Outcomes

Cancer therapies are currently limited to surgery, radiation, and chemotherapy. All three methods risk damage to normal tissues or incomplete eradication of the cancer. Nanotechnology offers the means to aim therapies directly and selectively at cancerous cells.

Nanocarriers: Conventional chemotherapy employs drugs that are known to kill cancer cells effectively. But these cytotoxic drugs kill healthy cells in addition to tumor cells, leading to adverse side effects such as nausea, neuropathy, hair-loss, fatigue, and compromised immune function. Nanoparticles can be used as drug carriers for chemotherapeutics to deliver medication directly to the tumor while sparing healthy tissue. Nanocarriers have several advantages over conventional chemotherapy. They can:

protect drugs from being degraded in the body before they reach their target.

enhance the absorption of drugs into tumors and into the cancerous cells themselves.

allow for better control over the timing and distribution of drugs to the tissue, making it easier for oncologists to assess how well they work.

Passive Targeting: There are now several nanocarrier-based drugs on the market, which rely on passive targeting through a process known as "enhanced permeability and retention." Because of their size and surface properties, certain nanoparticles can escape through blood vessel walls into tissues. In addition, tumors tend to have leaky blood vessels and defective lymphatic drainage, causing nanoparticles to accumulate in them, thereby concentrating the attached cytotoxic drug where it's needed, protecting healthy tissue and greatly reducing adverse side effects.

Active Targeting: On the horizon are nanoparticles that will actively target drugs to cancerous cells, based on the molecules that they express on their cell surface. Molecules that bind particular cellular receptors can be attached to a nanoparticle to actively target cells expressing the receptor. Active targeting can even be used to bring drugs into the cancerous cell, by inducing the cell to absorb the nanocarrier. Active targeting can be combined with passive targeting to further reduce the interaction of carried drugs with healthy tissue. Nanotechnology-enabled active and passive targeting can also increase the efficacy of a chemotherapeutic, achieving greater tumor reduction with lower doses of the drug.

Destruction from within: Moving away from conventional chemotherapeutic agents that activate normal molecular mechanisms to induce cell death, researchers are exploring ways to physically destroy cancerous cells from within. One such technology—nanoshells—is being used in the laboratory to thermally destroy tumors from the inside. Nanoshells can be designed to absorb light of different frequencies, generating heat (hyperthermia). Once the cancer cells take up the nanoshells (via active targeting), scientists apply near-infrared light that is absorbed by the nanoshells, creating an intense heat inside the tumor that selectively kills tumor cells without disturbing neighboring healthy cells. Similarly, new targeted magnetic nanoparticles are in development that will both be visible through Magnetic Resonance Imaging (MRI) and can also destroy cells by hyperthermia.

Key
Contacts

Dr. Piotr Grodzinski, Program Director, Nanotechnology in Cancer, Office of Technology and Industrial Relations, Office of the DirectorT: 301-496-1550grodzinp@mail.nih.gov